There is a need for new technologies to enable the analysis of the proteome. We propose to develop a novel technology for analyzing protease activity. Proteases are involved in the regulation of essential cellular processes and misregulation of proteolytic activity is involved in many diseases such as neurodegeneration, cardiovascular diseases, arthritis, Alzheimer's disease, cancer, and infectious diseases.
The protease activity profiling technology we are developing is useful for identifying new protease drug targets for drug development. It would help to elucidate the functional roles of specific proteases and may result in advances in the diagnosis and treatment of disease.
|Kukreja, Muskan; Shiryaev, Sergey A; Cieplak, Piotr et al. (2015) High-Throughput Multiplexed Peptide-Centric Profiling Illustrates Both Substrate Cleavage Redundancy and Specificity in the MMP Family. Chem Biol 22:1122-33|
|Shiryaev, Sergey A; Aleshin, Alexander E; Muranaka, Norihito et al. (2014) Structural and functional diversity of metalloproteinases encoded by the Bacteroides fragilis pathogenicity island. FEBS J 281:2487-502|
|Shiryaev, Sergey A; Remacle, Albert G; Chernov, Andrei V et al. (2013) Substrate cleavage profiling suggests a distinct function of Bacteroides fragilis metalloproteinases (fragilysin and metalloproteinase II) at the microbiome-inflammation-cancer interface. J Biol Chem 288:34956-67|
|Kozlov, Igor A; Thomsen, Elliot R; Munchel, Sarah E et al. (2012) A highly scalable peptide-based assay system for proteomics. PLoS One 7:e37441|
|Shiryaev, Sergey A; Thomsen, Elliot R; Cieplak, Piotr et al. (2012) New details of HCV NS3/4A proteinase functionality revealed by a high-throughput cleavage assay. PLoS One 7:e35759|